Human papillomavirus (HPV) infection is the central etiologic factor in the development of cervical and anal cancers. Recent data suggest that it is causally involved in 30 percent of oral cancers. Studies by our group and others have shown that 30-60 percent of sexually active college age women have cervical HPV infection. Our inner-city adolescence population, with its many high risk (HR) characteristics, has a prevalence of 63 percent cervical, 58 percent anal and 13 percent oral in our pilot study. The new Gardasil vaccine contains HPV 6, 11, 16 & 18 virus-like particles and has been shown to have a very high efficacy in HPV-DNA negative and HPV seronegative subjects. Little is know about its efficacy and effectiveness in a HR adolescent population, or in anal and oral mucosa. Despite these uncertainties physicians would find it unacceptable to not vaccinate high-risk adolescents, such as our population. The results of our research may demonstrate the need for a formal clinical trial of high risk adolescents. We therefore propose to study incidence of HPV infection following Gardasil vaccination in a prospective cohort of 1000 sexually active adolescent girls, ages 12-19 enrolled at the Mount Sinai AHC. We will collect baseline cervical, anal, oral specimens for HPV DNA testing and serum for HPV antibodies, the vaccine naive subjects will complete the 3 necessary vaccinations. They will be followed every 6 months for two years. Serum will be collected at baseline and 12 months. Our aims are to: 1) study the type-specific prevalence of HPV DNA in the cervix, anus, and oral cavity in high risk adolescents prior to vaccination including risk factors and co infection across sites; 2)determine the incidence of persistent HPV infection of the cervix following vaccination and contrast these rates with those expected based on the published vaccine trial results, by assessing incidence of persistent cervical infection in those adolescent women; 3)identify risk factors for an incidently developed persistent cervical infection with HPV, despite vaccination in those who were serologically and DNA negative for those types at baseline including infection in the anus or oral cavity and other risk factors; 4)study the incidence of persistent anal and oral infection with HPV following vaccination in this high risk cohort and the risk factors for infection with these HPV types in the anus, and to determine the incidence and risk factors for infection with phylogenetically- related and -unrelated HPV types in the anal and oral mucosa. [unreadable] [unreadable] [unreadable]